Hydrochloric Acid → Ethyl 2-[2-(2,4-difluorophenylamino)-5-fluoro-6-phenylthionicotinoyl]acetate

HRID 232470Notes

Reaction equation

HRID 232470 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[NH:9][C:10]1[N:23]=[C:22](OS(C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)(=O)=O)[C:21]([F:43])=[CH:20][C:11]=1[C:12]([CH2:14][C:15]([O:17][CH2:18][CH3:19])=[O:16])=O.C1([SH:50])C=CC=CC=1.C(N(CC)CC)C.Cl.[CH3:59][CH2:60][CH2:61][CH2:62][CH2:63][CH3:64]>CN(C)C=O.O.C(OCC)(=O)C>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[NH:9][C:10]1[N:23]=[C:22]([C:61]2[CH:60]=[CH:59][CH:64]=[CH:63][CH:62]=2)[C:21]([F:43])=[CH:20][C:11]=1[C:12]([CH2:14][C:15]([O:17][CH2:18][CH3:19])=[O:16])=[S:50]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 7969ThiophenolHCID 8058HexaneHCID 8471TriethylamineHCID 13849318Ethyl 2-[2-(2,4-difluorophenylamino)-5-fluoro-6-(2,4,6-triisopropylbenzenesulfonyloxy)nicotinoyl]acetate

Product 1

HCID 20031433Ethyl 2-[2-(2,4-difluorophenylamino)-5-fluoro-6-phenylthionicotinoyl]acetateYield 95.6%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

In 58 ml of N,N-dimethylformamide was dissolved 5.80 g of ethyl 2-[2-(2,4-difluorophenylamino)-5-fluoro-6-(2,4,6-triisopropylbenzenesulfonyloxy)nicotinoyl]acetate, and 1.24 g of thiophenol and 1.23 g of triethylamine were added thereto, after which the resulting mixture was subjected to reaction at room temperature for 4 hours. Subsequently, to the reaction mixture were added 400 ml of ethyl acetate and 200 ml of water, and the pH thereof was adjusted to 2.0 with 2N hydrochloric acid. The organic layer was separated, washed successively with 200 ml of water and 200 ml of saturated aqueous sodium chloride solution, and then dried over anhydrous magnesium sulfate. The solvent was removed by distillation under reduced pressure, and to the crystalline material thus obtained was added 50 ml of n-hexane, after which crystals were collected by filtration to obtain 3.99 g (yield 95.6%) of ethyl 2-[2-(2,4-difluorophenylamino)-5-fluoro-6-phenylthionicotinoyl]acetate. The physical properties of this compound were identical with those of the compound obtained in Example 19.

Workup

  1. additionwere added
  2. customafter which the resulting mixture was subjected to reaction at room temperature for 4 hours
  3. customThe organic layer was separated
  4. washwashed successively with 200 ml of water and 200 ml of saturated aqueous sodium chloride solution
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customThe solvent was removed by distillation under reduced pressure
  7. customto the crystalline material thus obtained
  8. filtrationafter which crystals were collected by filtration

Sources & evidence

ORD record
ord-602c4bd6e34540528ba5d883f1e8c9e6
Source dataset
uspto-grants-1989_07
Patent number
US04851535

Reaction notes

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